Nosocomial bacterial sepsis is a frequent and serious complication of the care of very low birth weight (VLBW) premature infants. Nosocomial sepsis is associated with higher mortality, as well as prolonged and more expensive hospital stays. The increased susceptibility of these extremely small babies to nosocomial bacterial sepsis is related to impaired immune function (Wilson, 1986), and to the invasive nature of the necessary supportive care. Recent evidence has been reported suggesting that immaturity of the skin may be a significant additional risk factor for developing nosocomial sepsis. Nopper and co-workers (1996) studied whether application of an emollient ointment (Aquaphor Original) would improve skin integrity and decrease transepidermal water loss in extremely premature babies. This study had an unanticipated additional finding of a lower incidence of nosocomial sepsis and/or meningitis in the group treated with an emollient ointment. The Neonatal Skin Care Study (NSCS) is designed to determine whether prophylactic application of Aquaphor reduces the incidence of nosocomial sepsis in babies of birth weight 501-1000 grams. The study will be conducted at participating centers in the Vermont Oxford Network, a non profit voluntary collaboration of NICU's. Infants meeting all eligibility criteria will be randomized to the Prophylactic Aquaphor Group or the Routine Skin Care Group. The Prophylactic Aquaphor Group will receive routine twice daily application of Aquaphor during the first 14 days of life. Both the Prophylactic Aquaphor Group and the Routine Skin Care Group may receive prn treatment with Aquaphor ointment for dermatitis or evidence of local skin injury. The primary outcome measure will be the incidence of mortality and/or nosocomial infection at 28 days of age. A 25% reduction in the outcome of mortality and/or nosocomial sepsis from 40% to 30% would require a sample size of 752 infants, therefore the target for enrollment is 800 infants. To date, over 50 centers have obtained institutional approval and have enrolled 250 infants.